The proposed program is directed at the development of new synthetic methods and the total synthesis of a wide range of biologically active mycotoxins and structurally related compounds. The synthetic strategies are chosen to provide efficient and stereoselective entries to target compounds in their natural absolute configurations. Our objective remains to develop efficient synthetic methods which would allow the preparation of natural products and their various synthetic derivatives in significant quantities for biological testing. Specific target molecules include the alpha-pyrone polyene mycotoxins, which are potent inhibitors of oxidative phosphorylation; erythromycin A, a representative member of clinically important macrolide antibiotics; polyhydroxy indolizidine alkaloids which are potent glycosidase inhibitors; related indolizidine and pyrrolizidine alkaloids, which have shown antitumor activity; several Dendrobatid alkaloids, which provide invaluable tools for the investigation of ion transport in many biological systems; morphinan alkaloids, potent analgesics; allene oxide-derived prostanoids, the biogenesis of which has fascinating evolutionary implications; ring construction of taxol which appears to be a promising cancer drug. An area of particular emphasis involves the stereocontrol of prochiral sp2 sites by an allylic oxygen substituent, and its application to the total synthesis of a wide range of multifunctional natural products and their various synthetic derivatives. We hope that our synthetic studies would eventually lead to mechanistic insights helpful in designing and rationalizing new stereoselective reactions.